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European Heart Journal Advance Access originally published online on February 15, 2006
European Heart Journal 2006 27(9):1061-1069; doi:10.1093/eurheartj/ehi760
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© The European Society of Cardiology 2006. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org

Baseline troponin level: key to understanding the importance of post-PCI troponin elevations

Wayne L. Miller1,*, Kirk N. Garratt1, Mary F. Burritt2, Ryan J. Lennon3, Guy S. Reeder1 and Allan S. Jaffe3

1 Cardiovascular Division, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN 55905, USA
2 Department of Laboratory Medicine and Pathology, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN 55905, USA
3 Division of Biostatistics, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN 55905, USA

Received 25 July 2005; revised 15 December 2005; accepted 13 January 2006; online publish-ahead-of-print 15 February 2006.

* Corresponding author. Tel: +1 507 284 3685; fax: +1 507 266 9142. E-mail address: miller.wayne{at}mayo.edu


   Abstract
Top
 Abstract
Introduction
 Methods
 Results
 Patients with elevated baseline...
 Discussion
 Acknowledgements
 References
 
Aims The adverse prognostic significance of biomarker elevations after percutaneous coronary intervention (PCI) is well established. However, often baseline troponin values are not included in the analysis or sensitive criteria are not employed. Accordingly, we assessed the timing and magnitude of post-PCI troponin T (cTnT) levels and their relationships to outcomes in patients with and without pre-PCI baseline cTnT elevations using a sensitive assay and sensitive cut-off values.

Methods and results cTnT was measured at baseline (pre-PCI), 8 and 16 h post-PCI in 2352 patients. A cTnT elevation was defined as ≥0.03 ng/mL. No baseline cTnT elevations were detected in 1619 patients undergoing mostly (97%) non-urgent procedures (cTnT=0.01±0.002 ng/mL; mean±SD). 733 patients had baseline cTnT elevations. Only the baseline troponin value had prognostic importance. Patients with elevated cTnT baseline levels had a higher overall cumulative 12-month death/MI rate of 11.1% compared with those without elevated baseline levels of 4.7% (P<0.05). Neither the timing nor the magnitude of the post-procedure cTnT elevations was predictive of long-term death/MI rates when baseline elevations were included in the analysis. Similar findings were observed for baseline creatine kinase-MB (CK-MB) levels. Late increases in cTnT levels (16 h post-PCI) presaged in-hospital events only.

Conclusion Long-term prognosis is most often related to the baseline pre-PCI troponin value and not the biomarker response to the PCI. These results support a re-evaluation of the use of biomarker data in relation to PCI.

Key Words: Troponin T • CK-MB mass • Baseline and peak biomarker values • PCI • Coronary artery disease


   Introduction
Top
 Abstract
 Introduction
Methods
 Results
 Patients with elevated baseline...
 Discussion
 Acknowledgements
 References
 
The adverse prognostic significance of myocardial biomarker elevations after catheter-based coronary interventions (percutaneous coronary intervention, PCI) is well established.1–11 However, the amount of injury in most cases is modest making it unlikely that prognosis is related to the extent of PCI-related injury. Thus, the mechanism for this effect is unknown. It has been suggested that elevations may reflect the extent of coronary artery disease, embolic events, stent expansion, or the lack of collateral perfusion to the area at risk12–17 as possible mechanisms of risk. However, some of these findings antedate the intervention and may be identifiable in many patients by baseline (pre-procedure) elevations in troponin. Elevations of troponin are known markers of unstable, extensive, and complex thrombotic coronary artery disease, and herald an adverse prognosis in patients with acute coronary syndromes.8,18,19 Most PCI outcome studies have not included the baseline troponin level as a co-variant and even when it has been measured and included in the analysis, low cut-off values that maximize prognostication have not been used.1,7,9–11,20–26 Accordingly, we evaluated consecutive patients enrolled in the Mayo Clinic PCI database to assess the influence of baseline troponin values using low and thus highly sensitive cut-off values and subsequent elevations of troponin after PCI on outcomes. In addition, we investigated whether the timing of troponin elevations post-PCI and the relationship between baseline troponin elevations and post-PCI creatine kinase-MB (CK-MB) mass elevations were of importance.


   Methods
Top
 Abstract
 Introduction
 Methods
Results
 Patients with elevated baseline...
 Discussion
 Acknowledgements
 References
 
A consecutive cohort of patients (n=2352) referred for elective or urgent (within 24–48 h of evaluation) coronary angiography and PCI with the diagnosis of progressive symptomatic coronary artery disease or acute coronary syndrome were studied prospectively. This group came from the total of 3321 PCIs done during the period August 1, 2000 to August 31, 2002. Five hundred and ninety-six were excluded because they had ST segment elevation acute myocardial infarctions. Of the remaining 2725 PCI, 86 (3.2%) were excluded because of the absence of a baseline troponin sample. Patients having baseline measurements but lacking complete post-PCI samples were not excluded (n=40). Thus, there remained 2639 procedures done on 2352 unique patients. We included only the earliest PCI per patient in the analysis.

Blood was drawn to measure cardiac troponin T (cTnT) and CK-MB mass at baseline (maximum of 72 h pre-procedure), 8 and 16 h post-PCI. An elevated cTnT was defined as a value ≥0.03 ng/mL per ESC/ACC guidelines27,28 and an elevated CK-MB mass was defined as ≥6.2 ng/mL.27,28 Patient data and follow-up were available via the Mayo percutaneous transluminal coronary angioplasty (PTCA) registry, a prospectively collected database. Patients were contacted by phone at 6 and 12 months post-PCI and yearly thereafter. At the time of the phone interview, the patients were asked about symptoms and hospitalization. If hospitalizations had occurred, we would review the records from that hospitalization after obtaining consent from the patient. If the patient was deceased, we would obtained from family members the date of death and cause of death if available. All patients who undergo PCI at our institution are followed-up by the same protocol and no patients were excluded because of lack of follow-up.

Integrilin or abciximab were most commonly used in conjunction with interventions when deemed clinically indicated. Standard recommended doses were used for 12–24 h post-PCI. All patients received aspirin (325 mg) before the intervention and patients receiving stent implantation received clopidogrel (300 mg) prior to stent placement. Subsequently, biomarker levels were determined at each predetermined time interval. cTnT assays were performed using a highly sensitive and precise third generation assay (Elecsys, Roche Diagnostics, Indianapolis, IN, USA). The cTnT assay has a coefficient of variability of 10% at a value of 0.035 ng/mL and 20% at 0.015 ng/mL. The limit of detection is ≤0.01 ng/mL. CK-MB mass was also measured on the Elecsys analyzer. This investigation was approved by the Mayo Foundation Institutional Review Board and included only patients who gave informed consent for research analysis as required by Minnesota Statute 144.335/ CRF 21 (Part 50).

Statistical analysis
Continuous data are presented as mean±standard deviation and compared using one-way analysis of variance (unless otherwise noted). Frequencies and percentages are used to summarize discrete variables, which are compared using Pearson's chi-squared test for nominal data and the Wilcoxon rank-sum test for ordinal data. In addition, higher cut-off values such as 0.10 ng/mL for cTnT were explored for both the pre- and post-PCI values. The date of discharge marked the beginning of the follow-up period. Kaplan–Meier methods were used to estimate survival rates. A significance level of <0.05 was used. All tests were two-sided. As this study is hypothesis generating, we have not adjusted any P-values for multiple hypothesis tests. Cox regression models (both simple and multivariable) were used to estimate hazard ratios. Multivariable regression models included variables typically associated with adverse events in this patient population.9 Biomarker levels were then added to the model. Biomarker values were log-transformed (base 2) to account for their skewed distribution and used as continuous variables. Thus, the resulting hazard ratios reflect the effect of a doubling in the biomarker. Linearity was assessed by visually inspecting Martingale residuals from an intercept only model against the logged troponin measures. There was no evidence of a need for a non-linear functional form. Proportional hazards assumptions were assessed by tests and plots based on weighted residuals.29 A likelihood ratio test was used to compare a model with only the baseline biomarker to a model with baseline, 8 and 16 h biomarkers (plus interactions between baseline and the two later measures). In this way, the additional prognostic information of the later biomarkers was assessed.


   Results
Top
 Abstract
 Introduction
 Methods
 Results
Patients with elevated baseline...
 Discussion
 Acknowledgements
 References
 
The baseline clinical characteristics of the 2352 patients included in the study with and without baseline elevations in cTnT are shown in Table 1. Those with cTnT elevations had more severe disease. The procedural treatment profile of patients undergoing PCI is also shown in Table 1. Sixty-five percent of these patients received IIb/IIIa inhibitor therapy. In 58% of patients, the procedure involved PTCA+stent placement, 11% underwent PTCA only, and 31% had stent placement only. There was no difference in the type of intervention used in patients with and without baseline cTnT elevations. More patients with baseline elevations in cTnT level underwent non-elective (PCI within 24–48 h of assessment) procedures than those without baseline elevation in cTnT (81 vs. 3%, P<0.001).


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  		Table 1 Patient and procedure characteristics by baseline troponin T level (ng/mL)

 
Post-PCI elevations
Early (8 h) cTnT peaks post-PCI were less common than late (16 h) peaks (15 vs. 42%, P<0.001) but tended to be of higher magnitude regardless of an elevated or normal pre-PCI cTnT level. When the baseline cTnT level was elevated, the frequency of peak elevations at 8 h was much greater (38 vs. 4%). Table 2 shows the values for cTnT and CK-MB at baseline and post-PCI based upon the presence or absence of pre-procedural elevation in cTnT. Patients with baseline elevations in cTnT had significantly higher values of both cTnT and CK-MB post-PCI.


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  		Table 2 Post-PCI troponin T levels in relation to baseline level

 
Post-PCI elevations of CK-MB (≥6.2 ng/mL) were much more frequent when the baseline cTnT was elevated. In patients without baseline elevation in cTnT, 10.1% had an elevated CK-MB at 8 h and 21.4% at 16 h post-procedure (Table 3). If cTnT level was elevated at baseline, many more patients had CK-MB elevations early after PCI (49.9% had CK-MB elevations at 8 h and 52.3% at 16 h, P<0.001). Overall, including elevations at both 8 and 16 h, 54% of patients with post-PCI elevations of CK-MB also had elevated baseline cTnT values.


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  		Table 3 Baseline troponin T levels and post-PCI CK-MB mass

 
Patients with normal baseline cTnT (<0.03 ng/mL)
Table 4 shows patient and procedure profiles for patients without baseline cTnT elevations (<0.03 ng/mL). Patients without changes in cTnT from baseline post-PCI were compared with those who had peak elevations at 8 and 16 h post-PCI. Troponin levels were not elevated at baseline in 1619 patients undergoing mostly (97%) non-urgent procedures (cTnT=0.01±0.002 ng/mL, mean±SD). Of these patients, 1396 had complete biomarker data (pre-procedure baseline, 8 or 16 h post-procedure) and thrombolysis in myocardial infarction (TIMI) grade 3 coronary blood flow post-procedure. No post-PCI cTnT elevations occurred in 756 (54%) patients. Sixty-two (5%) had peak values at 8 h (0.55±1.96 ng/mL) and 578 (41%) had cTnT peaks at 16 h post-PCI (0.17±0.36 ng/mL). GP IIb/IIIa inhibitors were more frequently used in those patients with post-PCI elevations in cTnT (66%) than those without elevations (55%, P<0.001). These patients did, however, also have more extensive coronary artery disease. Early cTnT peaks (8 h post-procedure) were not associated with a greater risk of long-term outcome of death/MI after multivariable correction when troponin was used as a continuous variable. When modelled at a higher cut-off value of ≥0.1 ng/mL, the HR was 2.21; CI 1.1–4.6; P=0.034.


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  		Table 4 Baseline troponin T levels <0.03 ng/mL

 
Late elevations in cTnT (16 h post-PCI) were associated with an overall increase in-hospital death/MI rate but not long-term events (Table 5; median follow-up 11.9 months). This likely reflects the acute result of the procedure itself, as when in-hospital events <24 h post-procedure were excluded, 16 h elevations in cTnT were no longer predictive of in-hospital death/MI (P=0.12; Table 5). There was no difference in long-term survival whether post-PCI cTnT levels were elevated above baseline or not (Figure 1; P=0.37).


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  		Table 5 Baseline troponin T levels <0.03 ng/mL

 

Figure 7601
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  		Figure 1 Kaplan–Meier survival curve analysis of patients with and without post-PCI troponin elevations when baseline (pre-procedure) troponin levels are <0.03 ng/mL.

 

   Patients with elevated baseline cTnT (≥0.03 ng/mL)
Top
 Abstract
 Introduction
 Methods
 Results
 Patients with elevated baseline...
Discussion
 Acknowledgements
 References
 
Table 6 shows the patient and procedure characteristics of the patients (n=733) with baseline elevations of cTnT ≥0.03 ng/mL (mean=0.58±1.03 ng/mL). Of the 603 patients with complete biomarker data (pre-procedure baseline, 8 and 16 h post-procedure) and demonstrated TIMI grade 3 coronary blood flow post-procedure, 119 (20%) had no further elevations of cTnT above the baseline level. Of the remaining patients, 231 (38%) demonstrated increased peak levels at 8 h (1.66±2.24 ng/mL) and 253 (42%) at 16 h (0.87±1.34 ng/mL) post-PCI. GP IIb/IIIa inhibitors were used more often in patients having post-procedure elevations above baseline in cTnT (77 vs. 62%, P<0.001). The extent of CAD was not different among the three patient groups. In those patients with elevated cTnT at baseline (≥0.03 ng/mL), late peak increases (16 h) but not early (8 h) peaks post-PCI were associated with increased (P<0.001) in-hospital events of death/MI (Table 7). These likely reflect events during the procedure itself, as most of these events occurred during the initial 24 h post-procedure. Neither 8 h nor 16 h peak increases were associated with a further increased risk of long-term events over and above the baseline elevation, even when only higher cTnT levels ≥0.1 ng/mL were used in the analyses (HR 1.12; CI 0.6–2.2; P=0.74). No difference in long-term survival was evident when patients with and without post-PCI cTnT levels above baseline were compared (Figure 2; P=0.22).


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  		Table 6 Baseline troponin T levels ≥0.03 ng/mL

 

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  		Table 7 Baseline troponin T levels ≥0.03 ng/mL

 

Figure 7602
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  		Figure 2 Kaplan–Meier survival curve analysis of patients with and without post-PCI troponin elevations when baseline (pre-procedure) troponin levels are ≥0.03 ng/mL.

 
Prognostic value of baseline vs. post-PCI cTnT elevation
Models with all three cTnT measures (baseline, 8 h, 16 h) did no better than baseline cTnT only models for both follow-up death (P=0.18) and death or MI (P=0.16). The baseline cTnT alone was significantly associated with follow-up events, even when adjusting for other risk factors (Table 8). Inclusion of the baseline cTnT values had a similar effect on post-PCI CK-MB mass values. In addition, similar to the prognostic value of baseline cTnT level, an elevated baseline CK-MB level was also shown to be predictive of death/MI (HR 1.12; CI 1.02–1.22, P=0.015; Table 9).


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  		Table 8 Baseline troponin and outcomes post-PCI

 

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  		Table 9 CK-MB–troponin interaction and post-PCI outcome

 

   Discussion
Top
 Abstract
 Introduction
 Methods
 Results
 Patients with elevated baseline...
 Discussion
Acknowledgements
 References
 
These data extend our understanding of post-PCI elevations in biomarkers. Our data show that it is the baseline elevations of cTnT which can be detected with sensitive assays and sensitive criteria that are predictive of events. When added to the analysis, post-PCI elevations of cTnT no longer have impact (Table 8). The same is true for post-PCI elevations of CK-MB. These effects may not be detected at baseline by CK-MB because of its limited sensitivity when compared with troponin. Only one other recent study has addressed this issue with sensitive troponin assays and sensitive cut-off values and made a similar point concerning the need for baseline values but lacked outcome data.30

Patients with elevated baseline cTnT values
Elevated baseline cTnT levels predicted a high cumulative 12-month death/MI rate of 11.1 vs. 4.7%, (P<0.05). Those with elevated baseline cTnT but no further increase post-PCI did comparatively well with a 7% death/MI rate at 12 months post-procedure but this was still nearly double the 4% event rate in those patients without baseline elevations and no post-PCI cTnT elevations. This trend did not reach statistical significance. These data suggest that the elevations in cTnT at baseline reflect the major cause of adverse prognosis seen in these patients and that additional values of cTnT and/or CK-MB do not add to that analysis. A similar trend was present for CK-MB but because of its reduced sensitivity compared with cTnT, a much smaller number of patients were involved.

Our data can neither define the mechanisms nor identify those patients who have post-PCI elevations due to rising levels at the time of PCI or who are simply marked as being at greater risk for cardiac injury by the baseline elevation. In patients with ACS, many of whom are included in this analysis, cTnT elevations at baseline (pre-procedure) are commonly associated with more diffuse coronary artery disease, increased thrombus, reduced TIMI flow grades, less collateral flow, and an adverse prognosis. In addition, these patients respond with an improved prognosis to more aggressive anti-coagulant therapies and an early invasive strategy31–34 as is the practice at our institution. The principles articulated should be applicable with most troponin assays but the cut-off values that are needed will obviously vary with the assay used.

The magnitude of peak cTnT elevations post-PCI, which has been suggested to be an adverse prognostic signal in many data sets,7,20–23,25,26 did not improve prognostication when the baseline troponin was elevated nor did it matter whether peak elevations were seen at 8 or 16 h except for the association of in-hospital complications when peak values occurred at 16 h.

These findings do not indicate that cardiac injury cannot occur during PCI when baseline values are elevated, only that their frequency and/or magnitude are insufficient to influence the prognosis of the cohort. These data do suggest, however, that the monitoring of post-PCI biomarkers when the baseline troponin is elevated may not be necessary.

Patients with normal baseline cTnT values
In this subset, the results are only slightly different. Peak elevations tended to occur late rather than early. Early elevations were uncommon and had no prognostic significance. When a cut-off value of 0.1 ng/mL was used, the P-value appeared to be significant. However, the fact that elevations could not be confirmed to be prognostic using continuous data makes this likely a statistical artefact related to multiple testing. When peak elevations occurred at 16 h post-PCI, as was more common in the group with normal baseline values, there was an association with elevations in in-hospital complications only.

CK-MB analysis
Baseline cTnT elevations also obviated the prognostic significance of post-PCI CK-MB elevations. The presence of CK-MB elevations was highly associated with baseline elevations of cTnT, but showed weaker prognostic value for long-term death/MI rates. Fifty-nine percent of those with post-PCI CK-MB elevations had baseline cTnT elevations and the magnitude of the CK-BM elevations was substantially greater and the timing was earlier (mean 7.42 ng/mL compared with 65.8 ng/mL for those peaking at 8 h and 9.79 ng/mL compared with 25.3 ng/mL for those peaking at 16 h). Nearly 50% of elevations occurred at 8 h, whereas in the absence of a baseline cTnT elevation, there was a 2:1 preponderance of late elevations. It may be that especially early elevations represent continued release of CK-MB in response to the initiating event that led to the need for PCI which was detected by the greater sensitivity of cTnT. In previous trials in which post-PCI values were found to be prognostic, there was invariably a gradient of risk with higher values being associated with greater risk.1,10,11,35,36 When baseline values for cTnT were included, a high cut-off value was often employed.1,20,23,25,26,37–43 If as suggested by our data, these post-PCI elevations were related to elevations in the baseline cTnT measurements, then assessment of post-PCI values may not be needed. Our data may also explain the confusion regarding the mechanisms involved which have been elusive and controversial.1,3,5,18,19,27,28

Implications
The practical clinical implications of these data for the diagnosis of post-PCI cardiac injury are significant. These findings question the utility of monitoring biomarkers post-PCI when the initial cTnT value is elevated. If confirmed in other data sets, these data would suggest that the routine monitoring of biomarkers post-PCI is not warranted to define short- and/or long-term prognosis if the baseline cTnT value is elevated. Looking for peak increases at 16 h may help to define in-hospital complications if not clinically overt. Although CK-MB values may more often be normal, they lack the sensitivity to be used in such a manner. It could be argued that such an approach should be extended to all patients who present acutely even if the initial cTnT value is not elevated, as it may be too early in some patients to know whether the value will be elevated. Absent an elevated baseline value, post-PCI values may be of value because elevations do correlate with in-hospital events when peak values occur at 16 h post-PCI. These data would also suggest a need to re-evaluate those therapeutic studies that have targeted the elimination of post-PCI biomarker elevations as a goal. Most data suggest that such interventions are far more effective in individuals who demonstrate elevated cTnT values at baseline.32,33,44,45

In conclusion, our data show for the first time that the presence and the degree of cTnT elevations pre-PCI are what predicts long-term events rather than the biomarker response to the PCI. On the basis of our data, re-evaluation of how biomarker data are used to assess prognosis in patients who undergo PCI seems warranted.


   Acknowledgements
Top
 Abstract
 Introduction
 Methods
 Results
 Patients with elevated baseline...
 Discussion
 Acknowledgements
References
 
The authors wish to thank the many physicians, nurses, and staff of the Mayo Cath Lab without whose help this study could not have been completed.

Conflict of interest: A.S.J. is a consultant and receives research support from Dad-Behring, Beckman-Coulter and Roche. He is or has been a consultant for many diagnostic companies that manufacture cardiac troponin assays. The other authors have no conflicts to declare.


   References
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 Abstract
 Introduction
 Methods
 Results
 Patients with elevated baseline...
 Discussion
 Acknowledgements
 References
 

  1. Cantor WJ, Newby LK, Christenson RH, Tuttle RH, Hasselblad V, Armstrong PW, Moliterno DJ, Califf RM, Topol EJ, Ohman EM for the SYMPHONY and 2nd SYMPHONY Cardiac Markers Substudy Investigators. Prognostic significance of elevated troponin I after percutaneous coronary intervention. JACC 2002; 39: 1738–1744.[Abstract/Free Full Text]
  2. Wu AH, Apple FS, Gilber WB, Jesse RL, Warshaw MM, Valdes R. National Academy of Clinical Biochemistry standards of laboratory practice: recommendations for the use of cardiac markers in coronary artery diseases. Clin Chem 1999; 45: 1104–1121.[Abstract/Free Full Text]
  3. Califf RM, Abdelmeguid AE, Kuntz RE, Popma JJ, Davidson CJ, Cohen EA, Kleiman NS, Mahaffey KW, Topol EJ, Pepine CJ, Lipicky RJ, Granger CB, Harrington RA, Tardiff BE, Crenshaw BS, Bauman RP, Zuckerman BD, Chaitman BR, Bittl JA, Ohman M. Myonecrosis after revascularization procedures. JACC 1998; 31: 241–251.[Abstract/Free Full Text]
  4. Tardiff BE, Califf RM, Tcheng JE, Lincoff AM, Sigmon KN, Harrington RA, Mahaffey KW, Ohman M, Teirstein PS, Blankenship JC, Kitt MM Topol EJ for the IMPACT-II Investigators. Clinical outcomes after detection of elevated cardiac enzymes in patients undergoing percutaneous intervention. JACC 1999; 33: 88–96.[Abstract/Free Full Text]
  5. Simoons ML, van den Brand M, Lincoff M, Harrington R, van der Wieken R, Vahanian A, Rutsch W, Kootstra J, Boersma E, Califf RM, Topol E. Minimal myocardial damage during coronary intervention is associated with impaired outcome. Eur Heart J 1999: 20: 1112–1119.[Abstract/Free Full Text]
  6. Jaffe AS, Ravkilde J, Roberts R, Naslund U, Apple FS, Galvani M, Katus H. It's time for a change to a troponin standard. Circulation 2000; 102: 1216–1220.[Free Full Text]
  7. Morrow DA, Cannon CP, Rifai N, Frey MJ, Vicari R, Lakkis N, Robertson DH, Hille DA, DeLucca PT, DiBattiste PM, Demopoulos LA, Weintraub WS, Braunwald E for the TACTICS-TIMI 18 Investigators. Ability of minor elevations of troponins I and T to predict benefit from an early invasive strategy in patients with unstable angina and non-ST elevation myocardial infarction. Results from a randomized trial. JAMA 2001; 286: 2405–2412.[Abstract/Free Full Text]
  8. Matetzky S, Sharir T, Domingo M, Noc M, Chyu KY, Kaul S, Eigler N, Shah PK, Cercek B. Elevated troponin I level on admission is associated with adverse outcome of primary angioplasty in acute myocardial infarction. Circulation 2000; 102: 1611–1616.[Abstract/Free Full Text]
  9. Cavallini C, Savonitto S, Violini R, Arraiz G, Blebani M, Olivari Z, Rubartelli P, Battaglia S, Niccoli L, Steffenino G, Ardissino D. Impact of the elevation of biochemical markers of myocardial damage on long-term mortality after percutaneous coronary intervention: results of the CK-MB and PCI study. Eur Heart J 2005; 26: 1494–1498.[Abstract/Free Full Text]
  10. Kizer JR, Muttrej MR, Matthai WH, McConnell J, Nardone H, Sonel AF, Keane MG, Wilensky RL. Role of cardiac troponin T in the long-term risk stratification of patients undergoing percutaneous coronary intervention. Eur Heart J 2003; 24: 1314–1322.[Abstract/Free Full Text]
  11. Nageh T, Sherwood RA, Harris BM, Byrne JA, Thomas MR. Cardiac troponin T and I and creatine kinase-MB as markers of myocardial injury and predictors of outcome following percutaneous coronary intervention. Int J Cardiol 2003; 92: 285–293.[CrossRef][ISI][Medline]
  12. Heeschen C, Van Den Brand MJ, Hamm CW, Simoons ML for the CAPTURE Investigators. Angiographic findings in patients with refractory unstable angina according to troponin T status. Circulation 1999; 100: 1509–1514.[Abstract/Free Full Text]
  13. Spadaro JJ, Philip AL, Tiefenbrunn AJ, Kurnik PB, Jaffe AS. Paucity of subtle myocardial injury after angioplasty delineated with MB CK. Catheterization and Cardiovascular Diagnosis 1986; 12: 230–234.[ISI][Medline]
  14. Vatner SF, Baig H, Manders WT, Maroko PR. Effects of coronary artery reperfusion on myocardial infarct size calculated from creatine kinase. J Clinic Invest 1978; 61: 1048–1056.[ISI][Medline]
  15. Okamatsu K, Takano M, Sakai S, Ishibashi F, Uemura R, Takno T, Mizuno K. Elevated troponin T levels and lesion characteristics in non-ST-elevation acute coronary syndromes. Circulation 2004; 109: 465–470.[Abstract/Free Full Text]
  16. Wong GC, Morrow DA, Murphy S, Kraimer N, Pai R, James D, Robertson DH, Demopoulos LA, DiBattiste P, Cannon CP, Gibson CM for the TACTICS-TIMI 18 Study Group. Elevations in troponin T and I are associated with abnormal tissue level perfusion: a TACTICS-TIMI 18 sub-study: Treat Angina with Aggrastat and Determine Cost of Therapy with an Invasive or Conservative Strategy-Thrombolysis in Myocardial Infarction. Circulation 2002; 106: 202–207.[Abstract/Free Full Text]
  17. Lindahl B, Diderholm E, Lagerqvist B, Venge P, Wallentin L the FRISC II Investigators. Mechanisms behind the prognostic value of troponin T in unstable coronary artery disease: A FRISC II substudy. J Am Coll Cardiol 2001; 38: 979–986.[Abstract/Free Full Text]
  18. Scirica BM, Morrow DA. Troponins in acute coronary syndromes. Progress in Cardiovascular Diseases 2004; 47: 177–188.[CrossRef][ISI][Medline]
  19. Ohman EM, Armstrong PW, Christenson RH, Granger CB, Katus HA, Hamm CW, O'Hanesian MA, Wagner GS, Kleiman NS, Harrell FE, Califf RM, Topol EJ, Lee KL for the GUSTO-IIa Investigators. Cardiac troponin T levels for risk stratification in acute myocardial ischemia. New Engl J Med 1996; 335: 1333–1342.[Abstract/Free Full Text]
  20. Bertinchant JP, Polge A, Ledermann B, Genet L, Fabbro-Peray P, Raczka F, Brunet J, Poirey S, Wittenberg O, Pernel I, Nigond J. Relation of minor cardiac troponin I elevation to late cardiac events after uncomplicated elective successful percutaneous transluminal coronary angioplasty for angina pectoris. Am J Cardiol 1999; 84: 51–57.[CrossRef][ISI][Medline]
  21. Bonz AW, Lengenfelder B, Strotmann J, Held S, Turschner O, Harre K, Wacker C, Waller C, Kochsiek N, Meesmann M, Neyses L, Schanzenbacher P, Ertle G, Voelker W. Effect of additional temporary glycoprotein IIb/IIIa receptor inhibition on troponin release in elective percutaneous coronary interventions after pretreatment with aspirin and clopidogrel (TOPSTAR Trial). J Am Coll Cardiol 2002; 40: 662–668.[Abstract/Free Full Text]
  22. Shyu KG, Kuan PL, Cheng JJ, Hung CR. Cardiac troponin T, creatine kinase and its isoform release after successful percutaneous transluminal coronary angioplasty with or without stenting. Am Heart J 1998; 135: 862–867.[CrossRef][ISI][Medline]
  23. Johansen O, Brekke M, Stromme JH, Valen V, Seljeflot I, Skjaeggestad O, Arnesen H. Myocardial damage during percutaneous transluminal coronary angioplasty as evidenced by troponin T measurements. Eur Heart J 1998; 19: 112–117.[Abstract/Free Full Text]
  24. Karim MA, Shinn M, Oskarsson H, Windle J, Deligonul U. Significance of cardiac troponin T release after percutaneous transluminal coronary angioplasty. Am J Cardiol 1995; 76: 521–523.[CrossRef][ISI][Medline]
  25. LaVecchia L, Bedogni F, Finocchi G, Mezzena G, Martini M, Sartori M, Castellani A, Soffiati G, Vincenzi M. Troponin T, troponin I and creatine kinase-MB mass after elective coronary stenting. Coronary Artery Disease 1996; 7: 535–540.[ISI][Medline]
  26. Ravkilde J, Nissen H, Mickley H, Andersen PE, Thayssen P, Horder M. Cardiac troponin T and CK mass release after visually successful percutaneous transluminal coronary angioplasty in stable angina pectoris. Am Heart J 1994; 127: 13–20.[CrossRef][ISI][Medline]
  27. The Joint European Society of Cardiology/American College of Cardiology Committee. Myocardial Infarction Redefined—A Consensus Document of The Joint European Society of Cardiology/American College of Cardiology Committee for the Redefinition of Myocardial Infarction. J Am Coll Cardiol 2000; 36: 959–969.[Free Full Text]
  28. Apple FS, Wu AHB, Jaffe AS. Guidelines for redefinition of myocardial infarction. How to use existing assays clinically and for clinical trials. Am Heart J 2002; 144: 981–986.[CrossRef][ISI][Medline]
  29. Grambsch PM, Therneau TM. Proportional hazards tests and diagnostics based on weighted residuals. Biometrika 1994; 81: 515–526.[Abstract/Free Full Text]
  30. Gustavsson CG, Hansen O, Frennby B. Troponin must be measured before and after PCI to diagnose procedure-related myocardial injury. Scan Cardiovasc J 2004; 38: 75–79.[CrossRef]
  31. Topol EJ, Moliterno DJ, Herrmann HC, Powers ER, Grines CL, Cohen DJ, Cohen EA, Bertrand M, Neumann FJ, Stone GW, DiBattiste PM, Yakubov SJ, DeLucca PT, Demopoulos L for the TARGET Investigators. Comparison of two platelet glycoprotein IIb/IIIa inhibitors, tirofiban and abciximab, for the prevention of ischemic events with percutaneous coronary revascularization. New Engl J Med 2001; 344: 1888–1894.[Abstract/Free Full Text]
  32. Newby LK, Ohman EM, Christensen RH, Moliterno DJ, Harrington RA, White HD, Armstrong PW, Van de Werf F, Pfisterer M, Hasselblad V, Califf RM, Topol EJ for the PARAGON-B Investigators. Benefit of glycoprotein IIb/IIIa inhibition in patients with acute coronary syndromes and troponin T-positive status. The PARAGON-B Troponin T Substudy. Circulation 2001: 103: 2891–2896.[Abstract/Free Full Text]
  33. Lincoff AM, Tcheng JE, Califf RM, Kereiakes DJ, Kelly TA, Timmis GC, Kleiman NS, Booth JE, Balog C, Cabot CF, Anderson KM, Weisman HF, Topol EJ for the EPILOG Investigators. Sustained suppression of ischemic complications of coronary interventions by platelet GP IIb/IIIa blockade with abciximab. One year outcome in the EPILOG Trial. Circulation 1999; 99: 1951–1958.[Abstract/Free Full Text]
  34. Lincoff AM, Califf RM, Anderson KM, Weisman HF, Aguirre FV, Kleiman NS, Harrington RA, Topol EJ for the EPIC Investigators. Evidence for prevention of death and myocardial infarction with platelet membrane glycoprotein IIb/IIIa receptor blockade by abciximab (c7E3 FaB) among patients with unstable angina undergoing percutaneous coronary revascularization. J Am Coll Cardiol 1997; 30: 149–156.[Abstract]
  35. Nallamothu BK, Chetcuti S, Mukherjee D, Grossman PM, Kline-Rogers E, Werns SW, Bates ER, Moscucci M. Prognostic implications of troponin I elevation after percutaneous coronary intervention. Am J Cardiol 2003; 91: 1272–1274.[CrossRef][ISI][Medline]
  36. Ricciardi MJ, Davidson CJ, Gubernikoff G, Beohar N, Eckman LJ, Parker MA, Bonow RO. Troponin I elevation and cardiac events after percutaneous coronary intervention. Am Heart J 2003; 145: 522–528.[CrossRef][ISI][Medline]
  37. Saadeddin SM, Habbab MA, Sobki SH, Ferns GA. Minor myocardial injury after elective uncomplicated successful PTCA with or without stenting: detection by cardiac troponins. Catheterization and Cardiovascular Intervention 2001; 53: 188–192.
  38. Fuchs S, Kornowski R, Mehran R, Lansky AJ, Satler LF, Pichard AD, Kent KM, Clark CF, Stone GW, Leon MB. Prognostic value of cardiac troponin-I levels following catheter-based coronary interventions. Am J Cardiol 2000; 85: 1077–1082.[CrossRef][ISI][Medline]
  39. Genser N, Mair J, Friedrich G, Talasz H, Moes N, Muhlberger V, Puschendorf B. Uncomplicated successful percutaneous transluminal coronary angioplasty does not affect cardiac troponin T plasma concentrations. Am J Cardiol 1996; 78: 127–128.[Medline]
  40. Kleiman NS, Lakkis N, Cannon CP, Murphy SA, DiBattiste PM, Demopoulos LA, Weintraub WS, Braunwald E TACTICS-TIMI 18 Investigators. Prospective analysis of creatine kinase muscle–brain fraction and comparison with troponin T to predict cardiac risk and benefit of an invasive strategy in patients with non-ST elevation acute coronary syndromes. J Am Coll Cardiol 2002; 40: 1044–1050.[Abstract/Free Full Text]
  41. Kugelmass AD, Cohen DJ, Moscucci M, Piana RN, Senerchia C, Kuntz RE, Baim DS. Elevation of the creatine kinase myocardial isoform following otherwise successful directional coronary atherectomy and stenting. Am J Cardiol 1994; 74: 748–754.[CrossRef][ISI][Medline]
  42. Abdelmeguid AE, Ellis SG, Sapp SK, Whitlow PL, Topol EJ. Defining the appropriate threshold of creatinine kinase elevation after percutaneous coronary interventions. Am Heart J 1996; 131: 1097–1105.[CrossRef][ISI][Medline]
  43. Thel MC, Califf RM, Tardiff BE, Gardner LH, Sigmon KN, Lincoff AM, Topol EJ, Kitt MM, Blankenship JC, Tcheng JE for the IMPACT-II Investigators. Timing of and risk factors for myocardial ischemic events after percutaneous coronary intervention (IMPACT II). Am J Cardiol 2000; 85: 427–434.[CrossRef][ISI][Medline]
  44. The EPIC Investigators. Use of a monoclonal antibody directed against the platelet glycoprotein IIb/IIIa receptor in high-risk coronary angioplasty. New Engl J Med 1994; 330: 956–961.[Abstract/Free Full Text]
  45. The EPILOG Investigators. Platelet glycoprotein IIb/IIIa receptor blockade and low-dose heparin during percutaneous coronary revascularization. New Engl J Med 1997; 336: 1689–1696.[Abstract/Free Full Text]

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